Carbinoxamine maleate is an antihistamine with anticholinergic (drying) and sedative effects. The molecule is chemically known as 2-[(4-chlorophenyl)-2-pyridinylmethoxy]-N,N-dimethylethanamine (Z)-2-butenedioate (1:1), and has the following chemical structure:

The compound was originally developed in the early 1950's by McNeil Laboratories. Beale et al., Clistin® Maleate: Clinical Appraisal of a New Antihistaminic, Jnl. Allergy 1954, 25:521-524. The product is currently marketed by Pamlab under the Palgic® brand as immediate release tablets and oral solution, for the treatment of seasonal allergic rhinitis. The recommended dose is 4 to 8 mg three or four times daily, which equates to a daily dose of from 12 to 32 mg. Teamm Pharmaceuticals markets a 12 hr. prolonged release carbinoxamine tablet as Histex CT that contains 8 mg of carbinoxamine maleate.
The pharmacokinetics of carbinoxamine maleate have been reported in the literature. Stockis et al., Arzneim.-Forsch 1992, 42(12):1478-81, studied the bioavailability of an 8 mg aqueous solution of carbinoxamine and an 8 mg retard capsule of carbinoxamine. The authors reported a Cmax of 24 and 16.9 ng/ml, Tmax of 3 and 8 hours, and a half-life of 10.6 and 14.5 hours for the solution and capsule, respectively. Stockis et al., Arzneim.-Forsch 1995, 45(9) 1009-1012, studied the bioavailability of a 4 mg retard capsule after a single and successive administrations, and reported a Cmax of 4.5 and 13.5, a Tmax of 6.2 and 4.8, and a half life of 30 and 22 for the 4 mg capsule after single and successive administrations, respectively.
Pseudoephedrine hydrochloride is an orally active sympathomimetic amine that exerts a decongestant action on the nasal mucosa. The molecule has the chemical name [S—(R*,R*)]-α-[1-(methylamino)ethyl]-benzenemethanol hydrochloride and the following chemical structure:

Pseudoephedrine has been shown to have a mean elimination half-life of 4-6 hours which is dependent on urine pH. The elimination half-life is decreased at urine pH lower than 6 and may be increased at urine pH higher than 8.
Dosage forms that combine pseudoephedrine with an antihistamine such as loratadine, cetirizine, fexofenadine, terfenadine, acrivastine or astemizole are known. In general, the amount of pseudoephedrine and antihistamine in these formulations is derived independently, based upon known dosing amounts for the individual ingredients. For example, Allegra-D® (12 hr) combines 60 mg of fexofenadine hydrochloride, which is the same dose employed in single ingredient 12 hr fexofenadine formulations, with 120 mg of pseudoephedrine, which is the same dose employed in 12 hr. single ingredient sustained release pseudoephedrine formulations. Similarly, Claritin D (12 hr) combines 5 mg of loratadine, which is ½ of the dose employed in single ingredient 24 hr loratadine formulations, with 120 mg of pseudoephedrine.
U.S. Pat. No. 6,051,585 to Weinstein et al. discloses a combination formulation containing pseudoephedrine, with limited duration of action, and an antihistamine for treating seasonal allergic rhinitis. U.S. Pat. No. 6,613,357 to Faour et al. discloses a combination osmotic device containing pseudoephedrine and an antihistamine for treating seasonal allergic rhinitis.
There exists a continuing need for effective prolonged release combination dosage forms for the relief of symptoms associated with allergic rhinitis and other respiratory conditions.